Barriers to Rotation in ortho-Substituted Tertiary Aromatic Amides: Effect of Chloro-Substitution on Resonance and Distortion

Planarity of the amide bond represents
one of the most widely recognized
properties of amides. Herein, we report a combined structural and
computational study on the effect of ortho-substitution on resonance
and barriers to rotation in tertiary aromatic amides. We demonstrate
that ortho-chloro substitution in a class of benzamides that are important
from the reactivity and medicinal chemistry perspective results in
increased barriers to rotation around both the N–C­(O) and C–C­(O)
axes. The effect of steric hindrance on structures, resonance energies,
barriers to rotation, and proton affinities is discussed. The present
study strongly supports the use of ortho-substitution in common benzamides
to strengthen amidic resonance.

酰胺键（amide bond）的平面性是酰胺类化合物最广为人知的固有性质之一。本文开展一项结合结构表征与计算模拟的联合研究，探讨邻位取代对叔芳酰胺（tertiary aromatic amides）中共轭共振效应及旋转能垒的影响。研究证实，一类在反应性与药物化学领域具有重要应用价值的苯甲酰胺（benzamides）类化合物，其邻位氯代取代可同时提升N–C(O)与C–C(O)双轴的旋转能垒。本文还讨论了空间位阻效应对分子结构、共振能（resonance energies）、旋转能垒（barriers to rotation）及质子亲和能（proton affinities）的影响。本研究有力支持了在常见苯甲酰胺类化合物中引入邻位取代基以强化酰胺共振效应的研究思路。